YokoCo

Discrimination of cues predicting non-nociceptive/nociceptive stimuli is essential for predicting whether a non-painful or painful stimulus will be administered and for eliciting placebo/nocebo (pain reduction/pain enhancement) effects. Dysfunction of the neural system involved in placebo effects has been implicated in the pathology of chronic pain, while female sex is one of the important risk factors for development of chronic pain in young adults. The dorsolateral prefrontal cortex (dl-PFC) is suggested to be involved in placebo effects and is sensitive to sex and age. In this study, to examine the neural mechanisms by which sex and age alter placebo and nocebo effects, we analyzed cerebral hemodynamic activities in the dl-PFC in different sex and age groups during a differential conditioning task. During the training session, two different sounds were followed by low- and high-intensity electrical shocks. In the following recording session, electrical shocks, the intensity of which was mismatched to the sounds, were occasionally administered to elicit placebo and nocebo effects. In young female participants, both placebo effects and hemodynamic responses to the conditioned sounds in the right dl-PFC were significantly lower than those in elderly female participants, while there were no age differences in male participants. The hemodynamic responses to the sound paired with the safe stimulus in the right dl-PFC were significantly correlated with placebo effects, except in the young female group. These results suggest that blunted placebo effects in the young female participants are ascribed to blunted responses to the sound associated with the safe stimulus in the right dl-PFC, and that sex- and age-related factors may alter the responsiveness of the right dl-PFC to associative cues predicting a safe stimulus.

Fibromyalgia (FM) is a disease characterized by the presence of chronic and widespread musculoskeletal pain, which causes a high negative impact on the quality of life (QoL). Although there are many studies about the QoL of patients with FM, it is unknown which variables have a main influence on it. Therefore, in the present study, we aimed to determine which FM symptoms predict a worse QoL and also to establish whether lifestyle and multi-medication are associated to QoL. We assessed a sample of 134 women with FM using a semi-structured clinical interview to explore lifestyle (diet, exercise, smoking) and medication use, and questionnaires to cover the main symptoms of this disease and QoL (SF-36). We found that the patients with FM had a poor QoL, being "physical pain" and "vitality" the most affected domains. A linear regression analysis showed that depression and anxiety assessed by HADS were the FM symptoms which most significantly predicted QoL, explaining 49% of the variance. Concerning lifestyle/medication influences, we found that multiple drug treatment and smoking also predicted a worse QoL (14%). Moreover, patients who practiced exercise regularly showed better QoL than patients who did not (regardless of the severity of FM). Thus, our results suggest that treatment strategies to improve QoL in FM should be focused on improving psychological distress, promoting regular exercise and reducing smoking and multi-medication. The data highlights the role of positive self-management practices to improve QoL in FM.

Leukotriene B4 (LTB4) is a potent lipid mediator involved in the recruitment and activation of neutrophils, which is an important feature of tissue injury and inflammation. The biological effects of LTB4 are primarily mediated through the high-affinity LTB4 receptor, BLT1. Postoperative incisional pain is characterized by persistent acute pain at the site of tissue injury and is associated with local inflammation. Here, we compared the role of LTB4-BLT1 signaling in postoperative incisional pain between BLT1-knockout (BLT1KO) and wild-type (BLT1WT) mice. A planter incision model was developed, and mechanical pain hypersensitivity was determined using the von Frey test before and after incision. Local infiltration of neutrophils and inflammatory monocytes was quantified by flow cytometry. Inflammatory cytokine levels in the incised tissue were also determined. Mechanical pain hypersensitivity was significantly reduced in BLT1KO mice compared to BLT1WT mice at 2, 3, and 4 days after incision. LTB4 levels in the tissue at the incision site peaked 3 hours after the incision. Infiltrated neutrophils peaked 1 day after the incision in both BLT1KO and BLT1WT mice. The accumulation of inflammatory monocytes increased 1-3 days after the incision and was significantly more reduced in BLT1KO mice than in BLT1WT mice. In BLT1KO mice, Interleukin-1β and Tumor Necrosis Factor-α levels 1 day after the incision were significantly lower than those of BLT1WT mice. Our data suggest that LTB4 is produced and activates its receptor BLT1 in the very early phase of tissue injury, and that LTB4-BLT1 signaling exacerbates pain responses by promoting local infiltration of inflammatory monocytes and cytokine production. Thus, LTB4-BLT1 signaling is a potential target for therapeutic intervention of acute and persistent pain induced by tissue injury.

Low vitamin D levels have been associated with musculoskeletal pain, cancer pain, chronic postoperative pain, and post-traumatic pain. However, their association with postoperative pain after video-assisted thoracoscopic surgery has not been explored. The aim of this study was to examine the association between vitamin D levels and postoperative pain after video-assisted thoracoscopic surgery.

Clinical data on cancer-induced pain (CIP) demonstrate widespread changes in sensory function. It is characterized in humans not only by stimulus-invoked pain, but also by spontaneous pain. In our previous studies in an animal model of CIP, we observed changes in intrinsic membrane properties and excitability of dorsal root ganglion (DRG) sensory neurons corresponding to mechanical allodynia and hyperalgesia, of which abnormal activities of Aβ-fiber sensory neurons are consistent in a rat model of peripheral neuropathic pain (NEP).

Abnormal angiogenesis and innervation in avascular discs during lumbar disc degeneration (LDD) cause severe back pain. These pathological alterations in the degenerating discs are induced by cytokines partially produced and secreted by inflammatory cells, among which macrophages are the most frequently ones detected at the legion site. However, the role of macrophages as well as their polarization in regulation of innervation and angiogenesis in the degenerating discs is unclear. In this study, we analyzed macrophages in the degenerating discs from patients and detected a specific macrophage subtype that expresses high levels of vascular endothelial growth factor A (VEGF-A). Co-expression of M2 macrophage markers in this macrophage subtype suggested that they were a M2d-like subtype. High levels of VEGF-A and genes associated with angiogenesis were also detected in LDD specimens compared to control heathy discs from a public database, consistent with our finding. Moreover, the levels of VEGF-A in disc macrophages were strongly correlated to the pain score of the examined patients, but not to the Thompson classification of the degeneration level of the patients. , overexpressing VEGF-A in macrophages increased the tube formation, proliferation and migration of co-cultured endothelial cells, and increased the innervation of embryonic spinal cord explant into the co-cultured area for macrophages and skeletal myocytes. , an orthotopic injection of adeno-associated virus carrying siRNA for VEGF-A under a macrophage-specific CD68 promoter significantly reduced the number of VEGF-A-positive disc macrophages and alleviated the pain in LDD-mice. Together, these data suggest that inhibition of angiogenetic potential of macrophages may reduce disc degeneration-associated pain through suppression of angiogenesis and innervation, as a promising therapy for LDD-associated pain.

Regional anesthesia is frequently employed in efforts to improve postoperative analgesia and reduce opioid requirements following abdominal surgery. The purpose of the current analysis was to determine if there was a difference in postoperative pain and opioid consumption between patients who underwent open total abdominal hysterectomy (TAH) and received ultrasound-guided bilateral transversus abdominis plane (TAP) blocks using either liposomal bupivacaine or ropivacaine. A single-center retrospective analysis was conducted of 215 patients from November 2018 through March 2020 who underwent an open TAH and received bilateral TAP blocks with either liposomal bupivacaine or ropivacaine. The primary outcome measure was opioid consumption at regular intervals until discharge, and the secondary outcome measures included pain scores, incidence of nausea/vomiting, and use of antiemetics at the same time intervals. Intraoperative opioid consumption and postanesthesia recovery unit opioid requirements were similar between the two groups. Opioid requirements at 24 hours ( < 0.04) and 48 hours ( < 0.01), as well as total morphine equivalent requirements ( < 0.05), were significantly lower in the liposomal bupivacaine group compared to the ropivacaine group. Patients undergoing open TAH who received liposomal bupivacaine TAP blocks required fewer postoperative opioids to achieve similar pain scores when compared to patients who received ropivacaine TAP blocks.

Patients with dysphagia often have an esophageal disorder. This case report describes a patient with persistent dysphagia and chest pain who had a normal esophagogastroduodenoscopy. Computed tomography of the chest with contrast revealed an aberrant right subclavian artery compressing the esophagus. A vascular procedure was performed and corrected the dysphagia. This case demonstrates that aberrant vessels can occasionally cause dysphagia.

We present a rare case of Mollaret's meningitis in a young patient with seven prior episodes of recurrent meningitis. The patient presented with headache, fever, neck stiffness, nausea, and vomiting. Brain imaging revealed no acute abnormalities. Lumbar puncture revealed elevated nucleated cells with lymphocytic predominance. The patient was started on antimicrobials including acyclovir. Cerebrospinal fluid polymerase chain reaction was positive for herpes simplex virus type 2. Her 2-day hospital course was uncomplicated, and she was discharged in good condition. Mollaret's meningitis, also known as recurrent benign lymphocytic meningitis, is a rare clinical disorder characterized by at least three recurrent episodes of meningitis associated with spontaneous recovery with or without antiviral therapy. Herpes simplex virus type 2 has frequently been implicated in the setting of this illness.